Immunoglobulin G3 from polyclonal human immunodeficiency virus (HIV) immune globulin is more potent than other subclasses in neutralizing HIV type 1.

Passive antibody prophylaxis against human immunodeficiency virus type 1 (HIV-1) has been accomplished in primates, suggesting that this strategy may prove useful in humans. While antibody specificity is crucial for neutralization, other antibody characteristics, such as subclass, have not been explored. Our objective was to compare the efficiencies of immunoglobulin G (IgG) subclasses from polyclonal human HIV immune globulin (HIVIG) in the neutralization of HIV-1 strains differing in coreceptor tropism. IgG1, IgG2, and IgG3 were enriched from HIVIG by using protein A-Sepharose. All three subclasses bound major HIV-1 proteins, as shown by Western blot assay and enzyme-linked immunosorbent assay. In HIV-1 fusion assays using X4, R5, or X4R5 envelope-expressing effector cells, IgG3 more efficiently blocked fusion. In neutralization assays with cell-free viruses using X4 (LAI, IIIB), R5 (BaL), and X4R5 (DH123), a similar hierarchy of neutralization was found: IgG3 > IgG1 > IgG2. IgG3 has a longer, more flexible hinge region than the other subclasses. To test whether this is important, IgG1 and IgG3 were digested with pepsin to generate F(ab')(2) fragments or with papain to generate Fab fragments. IgG3 F(ab')(2) fragments were still more efficient in neutralization than F(ab')(2) of IgG1. However, Fab fragments of IgG3 and IgG1 demonstrated equivalent neutralization capacities and the IgG3 advantage was lost. These results suggest that the IgG3 hinge region confers enhanced HIV-neutralizing ability. Enrichment and stabilization of IgG3 may therefore lead to improved HIVIG preparations. The results of this study have implications for the improvement of passive immunization with polyclonal or monoclonal antibodies and suggest that HIV-1 vaccines which induce high-titer IgG3 responses could be advantageous.

Human peripheral blood T cells, monocytes, and macrophages secrete macrophage inflammatory proteins 1alpha and 1beta following stimulation with heat-inactivated Brucella abortus.

Heat-killed Brucella abortus (HBa) has been proposed as a carrier for therapeutic vaccines for individuals with immunodeficiency, due to its abilities to induce interleukin-2 (IL-2) and gamma interferon (IFN-gamma) in both CD4(+) and CD8(+) T cells and to upregulate antigen-presenting cell functions (including IL-12 production). In the current study, we investigated the ability of HBa or lipopolysaccharide isolated from HBa (LPS-Ba) to elicit beta-chemokines, known to bind to the human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 and to block viral cell entry. It was found that human peripheral blood mononuclear cells secreted beta-chemokines following stimulation with HBa, and this effect could not be blocked by anti-IFN-gamma neutralizing antibodies. Among purified T cells, macrophage inflammatory protein 1alpha and 1beta (MIP-1alpha and MIP-1beta, respectively) secretion was observed primarily in human CD8(+) T cells. The kinetics of beta-chemokine induction in T cells were slow (3 to 4 days). The majority of beta-chemokine-producing CD8(+) T cells also produced IFN-gamma following HBa stimulation, as determined by triple-color intracellular staining. A significant number of CD8(+) T cells contained stored MIP-1beta that was released after HBa stimulation. Both HBa and LPS-Ba stimulated high levels of MIP-1alpha and MIP-1beta production in elutriated monocytes and even higher levels in macrophages. In these cells, beta-chemokine mRNA was upregulated within 30 min and proteins were secreted within 4 h of stimulation. The monocyte- and macrophage-derived beta-chemokines were sufficient to block CCR5-dependent HIV-1 envelope-mediated cell fusion. These data suggest that, in addition to the ability of HBa to elicit antigen-specific humoral and cellular immune responses, HBa-conjugated HIV-1 proteins or peptides would also generate innate chemokines with antiviral activity that could limit local viral spread during vaccination in vivo.

Management of neonatal ureteropelvic junction obstruction.

No topic in urology is more contentious than the management of neonatal ureteropelvic junction obstruction. Those favoring early diagnosis and correction of obstruction in early infancy cite excellent return of function and superior surgical results compared with delayed repair. Others believe that hydronephrosis improves or resolves with growth in many instances. In the most widely quoted series, almost all such patients improved. This article attempts to separate opinion from fact. The arguments for early surgery and for observation, even when obstruction has been diagnosed, are reviewed. Several experiences with long-term surveillance are summarized.

Long-term efficacy of simple behavioral therapy for daytime wetting in children.

PURPOSE: Behavioral therapy has proved benefit for children with daytime wetting but most studies have used biofeedback techniques and provide no long-term assessment of results. We previously reported similar results using simple behavioral therapy without biofeedback. We report the long-term efficacy of behavioral therapy for daytime wetting. MATERIALS AND METHODS: Our program of behavioral therapy included timed voiding, modification of fluid intake, positive reinforcement techniques and pelvic floor (Kegel) exercises to promote pelvic floor strengthening and relaxation. Questionnaires to assess therapeutic efficacy were mailed to patients who had completed therapy more than 1 year previously. RESULTS: A total of 48 patients responded. Mean ages at the time of the initial clinic visit and questionnaire were 8.2 and 12.9 years, respectively. Improvement in symptoms was noted in approximately 74% of the cases during the first year following therapy. At a mean of 4. 7 years after treatment 59.4% of the patients had improved daytime urinary control, 51.1% improved daytime urinary frequency and 45.6% improved daytime urinary urgency. The frequency of urinary tract infections decreased in 56.4% of the cases. Measures of psychological well-being were also noted to be improved in a majority of patients. A total of 77.3% of the patients stated that they would recommend the program to others. CONCLUSIONS: Simple behavioral therapy without biofeedback techniques is an effective and durable first line therapy for children with daytime wetting.

The incidence of nephrolithiasis in patients with spinal neural tube defects.

PURPOSE: Bladder stones are common in patients with spinal neural tube defects but there are little data on the incidence of renal calculi in this population. We examined the incidence, nature and risk factors of nephrolithiasis in our clinic population of patients with neural tube defects. MATERIALS AND METHODS: We retrospectively reviewed the charts and radiological studies of 327 patients followed at our neural tube defects clinic with routine radiological imaging of the urinary tract. Additional confirmatory studies were performed when stones were noted. RESULTS: Renal calculi were identified in 20 patients with neural tube defects (6.1%). The incidence of nephrolithiasis increased with age. Renal stones were noted in 19 patients (10.7%) 12 years old or older. Management of the stones in these patients resulted in overall 53% stone-free and 87% recurrence rates after intervention. Major risk factors for new and/or recurrent renal stone formation were bacteriuria in 95% of the cases, lower urinary tract reconstruction in 80%, pelvicalicectasis in 70%, vesicoureteral reflux in 65%, a thoracic level spinal defect in 60% and renal scarring in 55%. CONCLUSIONS: These data suggest that there is a higher incidence of nephrolithiasis in patients with neural tube defects than in the general population and the risk of stone recurrence is also elevated. Most patients with stones had undergone lower urinary tract reconstruction. Other risk factors were bacteriuria, pelvicalicectasis, vesicoureteral reflux and a thoracic level neural tube defect.

Orchiopexy for impalpable testis: high spermatic vessel division is a safe maneuver.

PURPOSE: This review was performed to assess the effect of protecting the collateral circulation between spermatic and vasal vessels by leaving a strip of peritoneum attached to the lower spermatic cord in patients in whom the spermatic vessels needed to be divided to bring the testis into good scrotal position. MATERIALS AND METHODS: Between 1983 and 1994, 22 boys were encountered in whom 1 testis was always normal in size and position, and the other was intra-abdominal and would not be in normal scrotal position after complete cord straightening. A strip of peritoneum had been left attached to the spermatic cord before full mobilization. After high division of the spermatic vessels the testes were brought in the mid scrotum during the same operation. RESULTS: All testes remained in scrotal position except 1 which retracted and was subsequently removed. None became atrophic. CONCLUSIONS: Division of the spermatic vessels, the Fowler-Stephens maneuver, can safely be performed during an initial operation as long as its possible need is anticipated, and the collateral circulation between the vasal vessels and spermatics is not disrupted. Secondary orchiopexy for inadequate cord length is now rarely required. This type of open orchiopexy for high impalpable testis is safe, is easy to learn, has no increased morbidity and is generally less expensive than a laparoscopic approach.

Sonographic appearance of the bladder after endoscopic incision of ureteroceles.

OBJECTIVE: Our intent was to describe the range of postoperative sonographic appearances of the bladder after endoscopic incision of ureteroceles. CONCLUSION: Preoperative and postoperative sonographic examinations of the bladder were reviewed in 14 patients (15 ureteroceles) who underwent endoscopic ureterocele incision. Five different appearances of the ureterovesical junction after endoscopic incision were found: a pseudomass (5/15), focal mucosal thickening (3/15), residual ureterocele with decrease in size (3/15), persistent unchanged ureterocele (1/15), and no residual abnormality (3/15). The most common postoperative sonographic appearance associated with development of vesicoureteral reflux was a mucosal pseudomass (4/6). The other bladder sonographic appearances had no correlation with development of reflux, degree of hydronephrosis, or success of the surgery.

Experience with transurethral incision of ureteroceles.

OBJECTIVES: The value of primary transurethral ureterocele incision was investigated in the treatment of ureteroceles in infants and children. METHODS: The charts and radiographic studies of 13 patients between the ages of 2 weeks and 8 years who underwent transurethral incision of 14 ureteroceles as primary surgical therapy at our institution were reviewed. RESULTS: 57% of the ureteroceles were intravesical and 43% extravesical. 64.3% were associated with the upper pole of a duplicated system. All 14 ureteroceles were associated with a functional renal moiety. Endoscopic incision achieved ureterocele decompression in 13 of 14 ureteroceles (93%). Preexisting hydronephrosis improved or resolved in 10 of 14 cases (71.4%). Renal function after decompression was not shown to be significantly altered or improved. 5 of 13 patients (38%) required definite surgical reconstruction for recurrent urinary tract infections, upper pole vesicoureteral reflux, hydronephrosis and lower pole vesicoureteral reflux within a mean follow-up period of 14 months. CONCLUSION: Transurethral incision has a limited role in the treatment of ureteroceles in children. In many or even most cases it cannot be expected to constitute long-term definite treatment for ureteroceles. It is mainly indicated in patients with urosepsis, prolapsing ureteroceles with functional bladder neck obstruction or massive reflux into other renal segments. In these settings it reliably achieves decompression and allows effective treatment of infection. The function of the previously obstructed renal segment can be reevaluated at later point in time to assess whether it should be saved. The delay permits interim growth that is likely to make bladder reconstruction easier.

Renal ultrasound changes after pyeloplasty in children with ureteropelvic junction obstruction: long-term outcome in 47 renal units.

PURPOSE: We evaluated the use of renal ultrasound for monitoring pyelocaliectasis after pyeloplasty in children. MATERIALS AND METHODS: Changes in pyelocaliceal dilatation following pyeloplasty were assessed by serial ultrasound. Of 104 children 0 to 12 years old who underwent pyeloplasty between 1982 and 1992, 44 (47 renal units) were monitored with serial ultrasound for at least 2 years (range 2 to 9, mean 3.8). Patient ages at pyeloplasty were 0 to 3 months (17), 4 to 12 months (8), 1 to 6 years (13) and 7 to 12 years (6). Preoperative and postoperative ultrasound was reviewed by a single pediatric radiologist blinded to the date of surgery. The degree of pyelocaliectasis was graded as 0 to 4 according to the classification of the Society for Fetal Urology. RESULTS: Preoperative ultrasound revealed grade 4 pyelocaliectasis in 26 kidneys (55%) and grade 3 disease in 21 (45%). Grade was the same or worse 1 month after pyeloplasty in the majority of kidneys (92%) studied at this interval. Of the 47 renal units assessed 43 (91%) showed improvement in pyelocaliectasis during postoperative followup. Only 38% of the kidneys improved during the first 6 months of followup, while 81% were improved 2 years postoperatively. Improvement to grade 0 or 1 dilatation occurred in only 9 kidneys (19%). The rate of resolution of pyelocaliectasis was not related to preoperative grade or patient age at pyeloplasty. CONCLUSIONS: Improvement on renal ultrasound after pyeloplasty appears to be gradual. Less than half of the patients had improvement in the initial 6 months after pyeloplasty and pyelocaliectasis rarely resolved completely. While renal ultrasound can provide an accurate and cost-effective means of monitoring children on a long-term basis after pyeloplasty, sonographic evaluation in the early postoperative period commonly shows increased or unchanged pyelocaliectasis.

Pediatric urology manpower report 1995. Ellen Shapiro on behalf of the American Association of Pediatric Urologists.

PURPOSE: The quality and efficiency of any health care system depend on an appropriate level of manpower. The manpower issues of tomorrow will be influenced by the number of physicians and specialists trained today. The objectives of this manpower survey of pediatric urologists in the United States were to determine anticipated manpower requirements and provide caveats related to the practice of pediatric urology. MATERIALS AND METHODS: A manpower questionnaire was distributed to pediatric urologists at the American Urological Association meeting in Las Vegas, Nevada in April 1995. Of the 234 distributed questionnaires 204 (87%) were completed and entered into a computer program. RESULTS: Of responding pediatric urologists 70% were younger than 50 years, 81% practiced full-time pediatric urology and 45% were university based. The rates of respondents indicating that their present workload was too busy, appropriate or not busy enough were 10, 70 and 20%, respectively. A total of 71% of respondents indicated that they would discourage a newly trained individual from setting up a practice in their area. Of practicing pediatric urologists 26% intended to retire within the next 10 years. In April 1995, 80 respondents (39%) representing 67 practices were considering adding an associate within the next 10 years. By the end of 1995 only 56 practices will remain that will add an associate within the next 10 years. A total of 82% of respondents believed that there was an excess number of pediatric urology training programs. CONCLUSIONS: The pediatric urology community presently trains 10 to 15 pediatric fellows per year. Based on the 1995 manpower survey, if this trend continues an excess of 40 to 90 pediatric urologists will be trained in the next 10 years. The conclusion that there is an overabundance of pediatric urologists in training is supported by the general consensus of practicing pediatric urologists. Policies related to the training of pediatric urology fellows and urology residents should depend, not on the manpower needs at individual medical centers, but on the collective needs of our specialty and the patients whom we serve.

Use of the expanded thoracoepigastric myocutaneous flap in the closure of cloacal exstrophy.

We describe the first reported use of an expanded thoracoepigastric myocutaneous flap in the closure of cloacal exstrophy. This approach offers several distinct advantages. The expander increases the available cutaneous surface area of the thoracoepigastric region, improves vascularity, induces a fibrous capsule that augments the abdominal wall, permits primary closure, and avoids prosthetic adjuncts that increase scarring and hinder delayed urinary tract reconstruction. Osteotomy and spica casting may be obviated by using this flap, but mesh may be required eventually. We anticipate its use in all future cases in which the abdomen cannot be closed safely at the primary procedure at this institution. This technique also should be considered for classic bladder exstrophy or any other large congenital or acquired defect of the lower abdomen.

A new approach to the closure of cloacal exstrophy.

Cloacal exstrophy patients are often difficult to reconstruct. Urinary continence is usually achievable only with a catheterizable stoma of some type. Since cloacal exstrophy is usually associated with omphalocele or gastroschisis, one-stage closure of the abdominal wall defect is frequently impossible. We prefer to incorporate the exstrophic large bowel, which separates the hemibladders, into the closed bladder as a sort of "natural" augmentation to maximize its volume for use as a continent reservoir. If a silastic "silo" or synthetic mesh is required to close the abdominal wall, excessive scarring occurs and later creation of a continent stoma is usually difficult and time-consuming. In all but those with the smallest abdominal wall defects we recommend that the omphalocele and upper abdominal wall be repaired first, replacing the evicted gut into the peritoneal cavity. During nutritional stabilization a tissue expander is placed under the superficial musculature of the chest wall. The flap is enlarged by gradual inflation of the tissue expander until it fills the abdominal wall defect left by subsequent closure of the cloacal exstrophy. The flap is then rotated inferiorly with blood supply intact at the time of bladder closure to make good the remaining abdominal wall defect. This flap improves the appearance of the abdominal wall and reduces scarring. Thus, this approach has the possibility of making subsequent operations to provide continence shorter, simpler, and more successful in most infants with cloacal exstrophy.

Are modern imaging techniques over diagnosing ureteropelvic junction obstruction?

Since the widespread use of real-time ultrasonography in the early 1980s, ureteropelvic junction obstruction has been diagnosed at earlier ages and prenatally on a presumptive basis. However, substantial controversy exists over the diagnosis and treatment of ureteropelvic junction obstruction. We conducted an epidemiological study to determine if modern imaging techniques are leading to the over diagnosis of ureteropelvic junction obstruction. Records were collected retrospectively from 3 hospitals serving 2 adjacent counties to determine the number of pyeloplasties performed in 1970 to 1992. The 2 university hospitals and 1 large private hospital provide a wide variety of services and choice of urologists, and so it was assumed that most patients requiring pyeloplasty in the area would be captured. Of the 555 pyeloplasties 240 (43%) were performed on children 12 years old or younger. Logistic regression analysis revealed an overall increase of pyeloplasties per year of 56.8% in 23 years, which was not markedly different from the population growth in the area in the same period (49.3%). A statistically significant increase in the number of pyeloplasties performed in the first year of life was noted. This trend appeared to begin in 1981: 8 pyeloplasties were performed in the first year of life between 1970 and 1980 compared to 91 between 1981 and 1992. Pyeloplasties in children 1 to 6 years old increased with time at a much lower rate that was not statistically significant and the number of pyeloplasties decreased in those 7 to 12 years old. Therefore, it appears that modern imaging techniques are not leading to an over diagnosis of ureteropelvic junction obstruction but to detection of the disease at an earlier age.

Acute pancreatitis in children: CT findings of intra- and extrapancreatic fluid collections.

PURPOSE: To determine the location and importance of fluid collections in children with acute pancreatitis. MATERIALS AND METHODS: The authors retrospectively reviewed the abdominal computed tomographic (CT) scans of 28 children with acute pancreatitis. CT scans were evaluated for pancreatic size and distribution of intra- and extrapancreatic fluid collections. Extrapancreatic fluid was classified as (a) peritoneal, (b) retroperitoneal, (c) mesenteric, or (d) ligamentous. RESULTS: Fourteen children (50%) had complicated pancreatitis associated with fluid collections. Intrapancreatic fluid was identified in only two patients (7%), whereas extrapancreatic fluid was seen in 14 (50%). Extrapancreatic fluid was most often seen in the anterior pararenal space, followed by the lesser sac, lesser omentum, and transverse mesocolon. The fluid collections diminished spontaneously in 11 patients (78%). Three patients with persistent fluid collections required surgical intervention for associated abnormalities. CONCLUSION: Intrapancreatic fluid collections are rare in children with pancreatitis. Extrapancreatic fluid collections tend to be extensive, but most diminish spontaneously.

Hydronephrosis. When is obstruction not obstruction?

It once was relatively simple for most urologists to diagnose ureteropelvic junction obstruction, and it was previously axiomatic that obstruction required repair to preserve and maximize renal function. Modern imaging studies have cast doubt on previously held concepts, leaving the clinician with an enigma. Prolonged follow-up of some non-operated cases has demonstrated late deterioration of function, further compounding the diagnostic uncertainty.

Bladder mucosal grafts for severe hypospadias: a successful technique.

Free grafts of bladder mucosa may be used to bridge long urethral defects in the repair of hypospadias. Strictures, which occur commonly at the proximal anastomotic site with the native meatus and where the bladder mucosa is exposed on the glans, have limited the use of the procedure. We have found that draining the proximal anastomosis prevents most strictures. When the distal most portion of the neourethra is formed from the skin of the ventral penile shaft and glans, no bladder mucosa is exposed and meatal stricture is thereby avoided.